ArticleProceedings of the National Academy of Sciences of the United States of America2010
Enhancement of GABA(A)-current run-down in the hippocampus occurs at the first spontaneous seizure in a model of temporal lobe epilepsy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- Ibogalogs induce antiseizure activity in rodents by a mechanism involving 5-HTBiochemical pharmacology · 2026Article
- Direct energy consumption by inhibitory GABAFrontiers in neuroscience · 2026Article
- Massive Activation of GABABiomolecules · 2025Review
- α4β2The Journal of physiology · 2025Article
- GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol.Life (Basel, Switzerland) · 2022Article
- Human iPSC Modeling of Genetic Febrile Seizure Reveals Aberrant Molecular and Physiological Features Underlying an Impaired Neuronal Activity.Biomedicines · 2022Article
- Levetiracetam Mechanisms of Action: From Molecules to Systems.Pharmaceuticals (Basel, Switzerland) · 2022Review
- GABACurrent topics in behavioral neurosciences · 2022Article
- Electrophysiology of ionotropic GABA receptors.Cellular and molecular life sciences : CMLS · 2021Review
- Dissecting the Molecular Determinants of GABABrain sciences · 2021Article
- Functional characterization of the antiepileptic drug candidate, padsevonil, on GABAEpilepsia · 2020Article
- Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?International journal of molecular sciences · 2020Review
- Use and Future Prospects of in Vivo Microdialysis for Epilepsy Studies.ACS chemical neuroscience · 2019Review
- Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Neurobiological Correlates of Alpha-Tocopherol Antiepileptogenic Effects and MicroRNA Expression Modulation in a Rat Model of Kainate-Induced Seizures.Molecular neurobiology · 2018Article
- Dynamic Changes of Astrocytes and Adenosine Signaling in Rat Hippocampus in Post-status Epilepticus Model of Epileptogenesis.Cellular and molecular neurobiology · 2018Article
- Astrocytic Atrophy FollowingFrontiers in molecular neuroscience · 2018Article
- Microdialysis Coupled with LC-MS/MS for In Vivo Neurochemical Monitoring.The AAPS journal · 2017Article
- Protective Effect of Resveratrol on the Brain in a Rat Model of Epilepsy.Neuroscience bulletin · 2017Article
- Differential modulation of GABAA and NMDA receptors by α7-nicotinic receptor desensitization in cultured rat hippocampal neurons.Acta pharmacologica Sinica · 2016Article
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of inhibitory signaling mediated by GABA(A) receptors. In particular, the use-dependent decrease (run-down) of the currents (I(GABA)) evoked by the repetitive activation of GABA(A) receptors is markedly enhanced in hippocampal and cortical neurons of TLE patients. Understanding the role of I(GABA) run-down in the disease, and its mechanisms, may allow development of medical alternatives to surgical resection, but such mechanistic insights are difficult to pursue in surgical human tissue. Therefore, we have used an animal model (pilocarpine-treated rats) to identify when and where the increase in I(GABA) run-down occurs in the natural history of epilepsy. We found: (i) that the increased run-down occurs in the hippocampus at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made), and then extends to the neocortex and remains constant in the course of the disease; (ii) that the phenomenon is strictly correlated with the occurrence of spontaneous seizures, because it is not observed in animals that do not become epileptic. Furthermore, initial exploration of the molecular mechanism disclosed a relative increase in alpha4-, relative to alpha1-containing GABA(A) receptors, occurring at the same time when the increased run-down appears, suggesting that alterations in the molecular composition of the GABA receptors may be responsible for the occurrence of the increased run-down. These observations disclose research opportunities in the field of epileptogenesis that may lead to a better understanding of the mechanism whereby a previously normal tissue becomes epileptic.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.